Survey of the use of warfarin and the newer anticoagulant dabigatran in patients with atrial fibrillation.

BACKGROUND: Oral dabigatran was recently approved as an alternative to warfarin for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Unlike warfarin, dabigatran has a fixed dosage and few drug interactions, and does not require anticoagulation monitoring or dietary restrictions. METHODS: This study aimed to describe and compare characteristics of patients with atrial fibrillation who used dabigatran or only warfarin. Patients with a self-reported diagnosis of atrial fibrillation aged ≥18 years who were receiving (or had received) warfarin or dabigatran completed an online survey. Differences in characteristics of dabigatran and warfarin users were tested using chi-squared tests and analysis of variance for categorical and continuous variables, respectively. RESULTS: Overall, 364 patients were surveyed (204 warfarin users, 160 dabigatran users). The mean age was 65.1 years, and 68.7% were male. Dabigatran users were more likely than warfarin users to be female (36.9% versus 27.0%) and to have experienced adverse events, including gastrointestinal bleeding, in the 3 months before the survey (21.9% versus 6.9%; P<0.05). Both groups reported high medication adherence (dabigatran users 0.65 versus warfarin users 0.63 missed doses/month). Dabigatran users were more likely than warfarin users to discuss treatment options with their physician before beginning therapy (36.9% versus 24.5%; P<0.05) and less likely to switch anticoagulant medication (10.7% versus 31.9%; P<0.05). Although dabigatran users were more likely to experience adverse events, they reported greater satisfaction with anticoagulation treatment than warfarin users. CONCLUSION: The efficacy and convenience reported by dabigatran users resulted in greater treatment satisfaction among dabigatran users, even though adverse events decreased it. Treatment strategies that minimize adverse events may improve treatment satisfaction and adherence among patients with atrial fibrillation.

Impact of co-morbidities and patient characteristics on international normalized ratio control over time in patients with nonvalvular atrial fibrillation.

This study determined the association between co-morbidities, including heart failure (HF) and time in therapeutic range (TTR), in patients with nonvalvular atrial fibrillation. Longitudinal patient-level anticoagulation management records collected from 2006 to 2010 were analyzed. Adult patients with nonvalvular atrial fibrillation who used warfarin for a 12-month period with no gap of >60 days between visits were identified. TTR <55% was defined as "lower" TTR. CHADS2 score of ≥2 was defined as "higher" CHADS2. Logistic regression analyses were conducted to determine the association between co-morbidities and TTR. A total of 23,425 patients met the study criteria. The mean age ± SD was 74.8 ± 9.7 years, with 84.8% aged ≥65 years. The most common co-morbidities were hypertension (41.7%), diabetes (24.1%), HF (11.7%), and previous stroke (11.1%). The mean TTR ± SD was 67.3 ± 14.4%, with 18.6% of patients in the lower TTR range. In multivariate analyses using age, gender, hypertension, diabetes, stroke, and region as covariates, HF (adjusted odds ratio [OR] 1.41, 95% confidence interval [CI] 1.28 to 1.56; p <0.001), diabetes (OR 1.28, 95% CI 1.19 to 1.38; p <0.001), and previous stroke (OR 1.15, 95% CI 1.04 to 1.27; p <0.001) were associated with lower TTR. In a second set of multivariate analyses using gender and region as covariates, a higher CHADS2 score was associated with lower TTR (OR 1.11, 95% CI 1.04 to 1.18; p <0.001). In conclusion, HF was associated with the greatest likelihood of a lower TTR, followed by diabetes, then stroke. Anticoagulation control may be more challenging for patients with these conditions.

Factors associated with warfarin discontinuation, including bleeding patterns, in atrial fibrillation patients.

OBJECTIVE: To determine risk factors for both warfarin discontinuation and bleeding in patients with atrial fibrillation (AF). METHODS: Data from the MarketScan database (January 2005-June 2008) were retrospectively analyzed for patients ≥18 years old who used warfarin continuously (≥2 prescriptions for 6 months) subsequent to an AF diagnosis. Patients were followed until one of the following endpoints occurred: warfarin discontinuation or end of the 30 month study period (whichever happened first). Recent bleeding was defined as occurring within 90 days before discontinuation. Drug interactions related to bleeding were defined as occurring within 120 days prior to bleeding. RESULTS: The study included 7971 eligible patients (mean age 67.8 years; 41.2% female). During follow-up, 51.7% of patients discontinued warfarin (P < .001). More patients with recent bleeding (61.8%) discontinued warfarin compared to patients without recent bleeding (51.3%). After adjustment, patients with recent bleeding were 35% more likely to discontinue warfarin compared to those without recent bleeding (relative risk = 1.35; CI: 1.16-1.58). Age >85 years and a history of ≥1 hospitalizations/emergency room visits were associated with an increased likelihood of discontinuation (P < .001). Female gender, daily dosage >5 mg, concomitant use of gastroprotective agents, and CHADS2 scores ≥1 were associated with a decreased likelihood of discontinuation (P < .05). CONCLUSIONS: Risk factors for warfarin discontinuation include older age, recent bleeding, and a high number of concomitant medications. Risk factors associated with bleeding events are older age, use of a warfarin-potentiating medication, previous bleeding, and higher CHADS2 scores.

Risk of hemorrhage and treatment costs associated with warfarin drug interactions in patients with atrial fibrillation.

BACKGROUND: Drug interactions with warfarin are common and may be responsible for increased patient morbidity and treatment costs. OBJECTIVES: To assess the usage patterns of drugs that potentiate warfarin's anticoagulant activity and discuss their associated relationship with both risk of hemorrhage and treatment costs among warfarin users with atrial fibrillation (AF). METHODS: A nested case-control study of long-term warfarin-treated AF patients was conducted using a health insurance claims database. Patients with a hemorrhagic event (cases) were matched to control patients using the incidence density sampling method. Drug-potentiating warfarin effects were identified within 30 days before the hemorrhagic event. Conditional logistic regression was used to calculate the association between use of potentiating drugs and hemorrhage risk. Mean treatment costs and CIs were calculated using the bootstrap method and tested using the t-test. Factors associated with treatment costs were determined using generalized linear models with the log-link function and γ distribution. RESULTS: Approximately 80% of AF patients were prescribed at least 1 warfarin-potentiating medication while taking warfarin. Patients who used these medications had a 26% higher risk of hemorrhage compared with those who did not use these drugs. Likelihood of hemorrhagic events was significantly increased with the use of potentiating drugs from the following therapeutic classes: anticoagulants (odds ratio [OR] = 1.91), anti-infectives (OR = 1.76), antiplatelets (OR = 1.56), and analgesics (OR = 1.33). The risk also increased when patients took ≥3 therapeutic classes of interacting medications (OR = 1.62-1.85). Among patients with a hemorrhagic event, patients who were prescribed potentiating drugs had higher hemorrhage-related treatment costs ($1359) compared with those patients without prescriptions for warfarin-potentiating drugs ($691; P < 0.001). CONCLUSIONS: Warfarin-potentiating drugs were commonly used among AF patients on warfarin. The use of potentiating drugs increased the risk of a hemorrhage, leading to higher treatment costs. More frequent monitoring or alternative anticoagulant therapies are needed to avoid frequent warfarin drug interactions.

Health care resource utilization and costs in a commercially insured population of patients with bipolar disorder type I and frequent psychiatric interventions.

BACKGROUND: Bipolar disorder type I (BP-I) is one of the most expensive behavioral diagnoses in the United States. Characterizing patient populations that consume significant resources would be useful for designing and implementing additional resources and targeted interventions to reduce the costs of BP-I. OBJECTIVE: This analysis compared the characteristics, health care resource utilization, and costs of commercially insured patients with BP-I (indicating a history of manic or mixed episodes) and frequent psychiatric interventions (FPIs) versus those without FPIs. METHODS: This retrospective study used data from commercial insurance claims to identify adults with FPIs (≥2 clinically significant events [CSEs]) or without FPIs during a 12-month identification period (year 1). CSEs included emergency department (ED) visits or hospitalizations with a principal diagnosis of BP-I, the addition of a new medication to the observed treatment regimen, or a ≥50% increase in BP-I medication dose. Demographic and clinical characteristics were evaluated during the identification period, and health care resource utilization and costs were evaluated during a 12-month follow-up period (year 2). RESULTS: Data from 7620 patients with FPIs and 11,571 without FPIs were included (women, 67.1% and 59.9%, respectively; P < 0.001). Of patients with FPIs in the identification period, 22.2% continued to have FPIs in the follow-up period. In the follow-up period, the group with FPIs had a greater proportion of patients with psychiatric-related inpatient hospitalizations (14.6% vs 2.8%) and ED visits (11.6% vs 2.7%) [corrected], a longer mean hospital length of stay (11.74% vs 8.24 days) [corrected], and greater adjusted mean psychiatric-related costs ($6617 vs $3276) and all-cause health care costs ($14,091 vs $9357) compared with the group without FPIs (all, P < 0.001). The risks for a psychiatric-related hospitalization and an ED visit during the follow-up period were significantly greater in the group with FPIs compared with the group without (odds ratios, 4.86 and 3.76, respectively; both, P < 0.01). CONCLUSIONS: In this retrospective analysis, FPIs were associated with a greater number of FPIs during follow-up, ∼2-fold the psychiatric-related costs, and 1.5-fold the all-cause health care costs compared with no FPIs. These data highlight the economic burden of FPIs and the potential for health care cost reductions from improved management options in these patients.

Predictors of medication nonadherence and hospitalization in Medicaid patients with bipolar I disorder given long-acting or oral antipsychotics.

PURPOSE: To assess rates and predictors of medication nonadherence and hospitalization among patients with bipolar I disorder. METHODS: This was a retrospective cohort analysis of Medicaid patients who were aged ≥ 18 years, had ≥ 1 inpatient or ≥ 2 outpatient medical claims indicating bipolar I disorder (ICD-9-CM codes 296.0x-296.1x, 296.4x-296.7x), and filled ≥ 1 prescription for antipsychotic medication between January 1, 2004, and December 31, 2006. Patients were followed for 1 year from the date of first (index) antipsychotic prescription. Patients were required to be continuously eligible for Medicaid without dual Medicare eligibility from 1 year before (baseline) through 1 year after (follow-up) index, and were required to receive ≥ 1 additional antipsychotic during follow-up. Descriptive statistics and predictors of medication nonadherence (medication possession ratio <0.8) and hospitalization were generated. RESULTS: A total of 9410 patients met study eligibility criteria with a mean age of 38 years; 74% were female and 75% were white. Approximately 31% and 57% had baseline diagnoses of substance abuse and other psychiatric conditions, respectively. During follow-up, roughly 60% of patients were nonadherent and 40% of patients were hospitalized for any reason (37% psychiatric-related). Multivariate analysis showed that new antipsychotic starts, younger patients, those with a baseline concomitant substance abuse diagnosis, those taking a baseline antidepressant, and those with a baseline psychiatric hospitalization had significantly higher risk of nonadherence. Baseline psychiatric hospitalization, baseline substance abuse or other psychosis diagnosis, baseline use of an anxiolytic, anticholinergic, or anticonvulsant, and nonadherence to therapy in the follow-up period were significant predictors of increased risk of hospitalization. LIMITATIONS: This analysis did not attempt to evaluate the complex relationships among treatment type, adherence, hospitalization, and other variables. CONCLUSIONS: Study results showed that the risk of nonadherence is relatively high and confirmed that nonadherence is associated with a greater risk of hospitalization.

Characteristics, healthcare utilization and costs of bipolar disorder type I patients with and without frequent psychiatric intervention in a Medicaid population.

OBJECTIVE: To compare characteristics, healthcare resource utilization and costs of Medicaid bipolar disorder (BPD) type I (BP-I) patients with and without frequent psychiatric intervention (FPI). METHODS: Adults with BP-I, ≥ 1 prescription claim for a mood stabilizer/atypical antipsychotic and 24 months' continuous medical/prescription coverage were identified (MarketScan* Medicaid database). Patients with ≥ 2 clinically significant events (CSEs) during a 12-month identification period had FPI. CSEs included emergency department (ED) visits or hospitalizations with a principal diagnosis of BPD, addition of a new medication to the first observed treatment regimen or ≥ 50% increase in BPD medication dose. Demographic and clinical characteristics were evaluated for the identification period, and healthcare utilization and costs for the 12-month follow-up. Multivariate generalized linear modeling and multivariate logistic regression, respectively, were used to evaluate the impact of FPI on all-cause and psychiatric-related costs and risk of psychiatric-related hospitalization and ED visit during follow-up. RESULTS: Of 5,527 BP-I patients, 53% had FPI. Relative to patients without FPI, those with FPI were younger and more likely to be female, had higher adjusted all-cause (+US$3,232, p < 0.001) and psychiatric-related (+US$2,519, p < 0.001) costs and higher risk of hospitalization (adjusted odds ratio [OR] = 3.681, 95% confidence interval [CI] = 2.85-4.75) and ED visit (OR = 3.094, 95% CI = 2.55-3.76). LIMITATIONS: Analysis used a convenience sample of Medicaid enrollees in several geographically dispersed states, limiting generalizability. Analyses of administrative claims data depend on accurate diagnoses and data entry. CONCLUSION: BP-I patients with FPI incurred significantly higher healthcare resource utilization and costs during the follow-up period than those without FPI.